Non-protein antigens such as polysaccharides and lipids induce antibody responses without the need for T cells and are therefore referred to as T-independent (TI) antigens. However, because of the lack of involvement of T cell help, most TI antigens are relatively poor immunogens. In general, responses to TI antigens consist of IgM antibodies of low affinity, and do not show significant heavy chain class switching, affinity maturation, or memory. The practical significance of TI antigens is that many bacterial capsular and cell wall polysaccharides belong to this category and are therefore relatively poor at eliciting humoral immunity.
Young children and the elderly are particularly susceptible to life-threatening infections with encapsulated bacteria such as pneumococcus and meningococcus. It has been estimated by the Centers for Disease Control that in the U.S. per year, Streptococcus pneumoniae causes 3,000 cases of meningitidis, 50,000 cases of bacteremia, 500,000 cases of pneumonia, and 7 million cases of otitis media (middle ear infection). The World Health Organization has estimated that worldwide, this organism causes 100 million cases per year with 10 million deaths per year. Similarly, Neisseria meningiditis is the leading cause of meningitis in children and young adults with 2,600 cases/year in the U.S., 310,000 cases and 35,000 deaths per year worldwide.
Polysaccharide vaccines for inducing immunity to pathogens such as S. pneumoniae and N. meningiditis are available, but they are generally ineffective in children less than 2 years of age and are of limited efficacy in older individuals. In addition, in all recipients the vaccines, even in conjugate form, induce limited isotype switching. Clearly, alternative approaches for vaccination against pathogens having TI antigens are needed.